Transplant recipients are at significantly increased risk for developing non-melanoma skin cancer: compared to the general population, they have a 60-250 fold increased risk of developing aggressive, life- threatening squamous cell carcinoma. Indeed, it is estimated that 27% of Australian heart transplant recipients who'd survived greater than 4 years had squamous cell carcinoma as the cause of death. It is clear that the immunosuppression required to prevent rejection is a major factor in the increased skin cancer risk, and reducing these medications can be beneficial. However, any reduction in immunosuppression increases the risk of transplant rejection. Thus, any new preventive or treatment strategies must work in concert with the immunosuppressive medications. Black raspberries contain several anti-oxidants with anti-inflammatory and anti-cancer properties. Indeed, our preliminary data indicate that topical black raspberry extracts (BRE) significantly inhibit UV-induced inflammation and carcinogenesis. We hypothesize that BRE inhibits inflammation through inhibiting oxidative pathways. This hypothesis will be tested in the following two Specific Aims. In specific aim 1, we will determine the effects of BRE on neutrophils and the PI3K pathway in UVB-induced inflammation and carcinogenesis. Specific Aim 2 will determine if BRE are able to reduce the exacerbated UVB-induced inflammation and carcinogenesis caused by cyclosporin. The results from these studies will provide basic mechanistic information on how topical BRE inhibit inflammation and carcinogenesis and begin to determine if BRE may be effective as a chemopreventive in transplant patients and other immunosuppressed individuals. [unreadable] [unreadable] [unreadable]